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Biomedical subjects

J Yu

Publications and source records attributed to J Yu.

At least 55 records · Page 3Linked to original sources

Interethnic variability of ERCC2 polymorphisms.

Excision Repair Cross-Complementing Rodent Repair Group 2 (ERCC2) plays an important role in DNA repair by eliminating bulky DNA adducts produced by platinum agents during the nucleotide excision repair pathway. Several studies have associated polymorphisms in ERCC2 with response to platinum therapy, lung cancer risk, and DNA repair capacity. This study examined ERCC2 polymorphisms and haplotype structure across 18.9 kb in 95 European, 95 African, and 95 Asian individuals. Single-nucleotide polymorphisms (SNPs) (ERCC2 -9164 A>T, -1989 A>G, -516 G>A, 468 C>A [Arg156Arg], 1737 C>T [Val579Val], 2133 C>T [Asp711Asp], and 2251 T>G [Lys751Gln]) were mined and mapped using Golden Path, PolyMAPr, and Promolign. Genotyping was performed using PCR and pyrosequencing. Allele frequencies ranged from 0 to 0.47 (Europeans), 0.05 to 0.72 (Africans), and 0 to 0.47 (Asians). The synonymous cSNP at codon 579 could not be confirmed in our populations. There were significant differences in haplotype structure and frequency between populations. This information on ERCC2 genomic structure will allow the construction of definitive studies to clarify the clinical role of this important gene.

Adult↗

Aflatoxin biosynthesis gene clusters and flanking regions.

AIMS: To compare the biosynthetic gene cluster sequences of the main aflatoxin (AF)-producing Aspergillus species. METHODS AND RESULTS: Sequencing was on fosmid clones selected by homology to Aspergillus parasiticus sequence. Alignments revealed that gene order is conserved among AF gene clusters of Aspergillus nomius, A. parasiticus, two sclerotial morphotypes of Aspergillus flavus, and an unnamed Aspergillus sp. Phylogenetic relationships were established using the maximum likelihood method implemented in PAUP. Based on the Eurotiomycete/Sordariomycete divergence time, the A. flavus-type cluster has been maintained for at least 25 million years. Such conservation of the genes and gene order reflects strong selective constraints on rearrangement. Phylogenetic comparison of individual genes in the cluster indicated that ver-1, which has homology to a melanin biosynthesis gene, experienced selective forces distinct from the other pathway genes. Sequences upstream of the polyketide synthase-encoding gene vary among the species, but a four-gene sugar utilization cluster at the distal end is conserved, indicating a functional relationship between the two adjacent clusters. CONCLUSIONS: The high conservation of cluster components needed for AF production suggests there is an adaptive value for AFs in character-shaping niches important to those taxa. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first comparison of the complete nucleotide sequences of gene clusters harbouring the AF biosynthesis genes of the main AF-producing species. Such a comparison will aid in understanding how AF biosynthesis is regulated in experimental and natural environments.

Aflatoxins↗

Coincidence of atopy profile in terms of monosensitization and polysensitization in children and their parents.

BACKGROUND: Results from epidemiologic studies have shown that childhood atopy is probably a hereditary disorder, because the offspring of affected parents have a higher risk of developing atopy. Among the atopic population, some subjects are sensitized to only one class of allergens (monosensitized), while other subjects are sensitized to more than one class of allergens (polysensitized). The aim of this study was to investigate whether atopy profile (monosensitization/polysensitization) in children is linked to the same conditions in their parents. METHODS: We evaluated sensitization to five classes of aeroallergens (house dust mites, animal danders, pollens, molds, and cockroach) by skin prick testing in a group of 494 children with suspicious allergic symptoms and in their parents. RESULTS: The frequency of parental atopy was highest (51.6%) in polysensitized children (n = 189), intermediate (37.1%) in monosensitized children (n = 178), and was lowest (22.4%) in nonsensitized children (n = 127). The proportion of polysensitized subjects among atopic parents was significantly higher for polysensitized children (45.6%) than for monosensitized children (31.1%). Polysensitized children were found to more frequently have one or both parents polysensitized (32.3%, 7.4%) than monosensitized children (18.5%, 2.2%) with odds ratios of 2.09 (95% CI: 1.29-3.40) and 3.48 (1.12-10.78), respectively, whereas the likelihood of having one or two monosensitized parents was not increased for polysensitized children. CONCLUSION: Our data suggest a familial coincidence of atopy profile in terms of monosensitization and polysensitization, although the relative importance of genetic or environmental influence should be studied further.

Allergens↗

Birth month and sensitization to house dust mites in asthmatic children.

BACKGROUND: Early exposure to high quantities of allergen has an important role in the incidence of atopic sensitization. In fact, subjects sensitized to house dust mites (HDMs) have a significantly higher proportion of births in the season when HDMs are most abundant. OBJECTIVE: The aim of this study was to investigate whether birth month patterns differ for asthmatic patients sensitized only to HDMs and for those sensitized to HDMs and other allergen(s). METHODS: Among 2225 patients with asthma, aged 10-16 years, 1642 sensitized to HDMs were identified by skin prick testing. This group was composed of patients sensitized only to HDMs (n = 715) and patients sensitized to HDMs and other allergen(s) (n = 927). The birth month distributions of the group of HDM-sensitive asthmatics or its subgroups were compared with that of a reference population (total live births in the same years as the studied subjects). The risk ratio of a given birth month in relation to all the other months was calculated as an odds ratio (OR) with the corresponding 95% confidence interval (CI). RESULTS: A significant difference in birth month distribution was observed for HDM-sensitive asthmatics (chi(2) = 23.6, P = 0.015), with higher rates of birth in August (OR: 1.23, 95% CI: 1.04-1.46) and September (1.24, 1.04-1.46). When the two subgroups were analyzed separately, significantly more births were noted in August (1.34, 1.06-1.71) and September (1.34, 1.05-1.70) for those sensitized only to HDMs, whereas no such birth month preference was observed for those sensitized to HDMs and other allergen(s). CONCLUSIONS: The HDM-positive asthmatics showed a greater proportion of births in August and September, which correspond to high HDM exposure. However, this birth month pattern was evident in asthmatic-sensitive only to HDMs, but was not observed in those sensitive to HDMs and other allergen(s).

Adolescent↗

Comparison of the effects of isoflurane and sevoflurane on protein tyrosine phosphorylation-mediated vascular contraction.

BACKGROUND: Isoflurane induces greater effects on vasodilation and decreasing blood pressure than sevoflurane. Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an important role in regulating vascular smooth muscle contraction. The aim of the present study was to compare the effects of isoflurane and sevoflurane on tyrosine phosphorylation-mediated vascular constriction, by assessing the degree of sodium orthovanadate (Na(3)VO(4), tyrosine phosphatase inhibitor)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle. METHODS: Na(3)VO(4)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle were measured in the presence of genistein, a tyrosine kinase inhibitor, and different concentrations of isoflurane and sevoflurane, using isometric force measurement and Western blot, respectively. RESULTS: Na(3)VO(4) (10(-4) M) induced sustained contraction and tyrosine phosphorylation of substrates that were both markedly attenuated in the presence of genistein (5 x 10(-5) M). Isoflurane and sevoflurane dose-dependently (1, 2, 3 MAC) attenuated the Na(3)VO(4)-induced contraction (P < 0.05-0.005, n = 8), with a greater degree of inhibition by isoflurane than sevoflurane at 2 MAC (P < 0.01) and 3 MAC (P < 0.05). Both anesthetics also attenuated the total band density of the Na(3)VO(4)-induced, tyrosine-phosphorylated substrates in a concentration-dependent manner (P < 0.05-0.005, n = 4), with much greater attenuation by isoflurane than sevoflurane at 1 and 2 MAC (P < 0.05), respectively. CONCLUSION: The results of the present study demonstrate that isoflurane exhibits a greater degree of inhibition on the Na(3)VO(4)-stimulated contraction and protein tyrosine phosphorylation of rat aortic smooth muscle compared with sevoflurane. These findings suggest that isoflurane depresses the protein tyrosine phosphorylation-mediated contraction of vascular smooth muscle to a greater degree than sevoflurane.

Anesthetics, Inhalation↗

New genotype of avian influenza H5N1 viruses isolated from tree sparrows in China.

The 2004 outbreaks of highly pathogenic avian influenza H5N1 disease in China led to a great poultry loss and society attention. A survey of avian influenza viruses was conducted on tree sparrows (Passer montanus) collected in China in 2004. Four viruses were isolated from free-living tree sparrows. The results of the whole-genome analysis indicated that an H5N1 virus with a new genotype is circulating among tree sparrows. The hemagglutinin and neuraminidase genes of the new genotype were derived from Gs/Gd/96-like viruses and the nuclear protein gene descended from the 2001 genotype A H5N1 viruses, while the other inner genes originated from an unknown influenza virus. In experimental infection, all four viruses were highly pathogenic to chickens but not pathogenic to ducks or mice. The four tree sparrow viruses were different from the 2003 tree sparrow strain (genotype Z) in Hong Kong. The results suggested that H5N1 viruses might be distributed widely in tree sparrows.

Animals↗

Polymorphisms in the bovine leptin promoter associated with serum leptin concentration, growth, feed intake, feeding behavior, and measures of carcass merit.

Leptin is the hormone product of the obese gene synthesized and secreted predominantly by white adipocytes. It functions as a lipostatic signal regulating BW, food intake, energy expenditure, reproduction, and certain immune system functions. Although previous studies have identified polymorphisms in the coding regions of the leptin gene in cattle that show considerable associations with feed intake, milk quality and quantity, and carcass fatness, no such associations have been reported for the leptin promoter. The current study reports associations between SNP in the 5' untranslated promoter region of the bovine leptin gene with serum leptin concentration, growth, BW, feed intake, feeding behavior, and carcass merit in hybrid cattle (n = 150). The study showed that animals with the TT genotype of a less frequent cytosine/thymine (C/ T) substitution (UASMS2; frequency of thymine allele equals 0.21) detected at position 528 in the bovine leptin promoter (GenBank Accession No. AB070368) show 48 and 39% increases in serum leptin concentration (P < 0.001), 39 and 31% increases in backfat thickness (P < 0.001), and 13 and 9% increase in marbling score (P = 0.01), compared with CC or CT genotypes, respectively. Animals with the TT genotype also show significantly higher feed intake (P < 0.001), growth rate, metabolic BW (P < 0.05), and live weight at slaughter (P < 0.10). Animals with the GG genotype of a more frequent cytosine/guanine (C/G) substitution (UASMS3; frequency of G allele equals 0.59) at position 1759 in the bovine leptin promoter (GenBank Accession No. AB070368) also show higher feed intake (P = 0.001), growth rate (P < 0.10), and BW (P < 0.01). The thymine allele of UASMS2 and the guanine allele of UASMS3 were separately associated with higher feeding duration (P < 0.05). The two SNP show significant linkage disequilibrium and could also be relevant in predicting other characteristics, such as milk yield and quality in cattle. These results, however, represent the initial associations of the polymorphisms with these traits, and further efforts are required to validate these findings in other populations.

Animals↗

Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle.

Studies with different populations are required to properly characterize the robustness of associations of polymorphisms in candidate genes with economically important traits across beef cattle populations before this sort of genetic information can be used efficiently in breeding and management decisions. The objective of this study was to evaluate the association of previously reported SNP in the bovine leptin gene with carcass and meat quality traits from a large sample of crossbred beef cattle. Five SNP (UASMS1, UASMS2, UASMS3, E2JW, and E2FB) were genotyped on 1,111 crossbred bulls, heifers, and steers. The measured traits included fat, lean, and bone yield (%) by partial rib dissection, grade fat, LM area, HCW, quality grade, LM i.m. fat, and tenderness evaluation of LM and semitendinosus muscle. Only four SNP were analyzed (UASMS1, UASMS2, E2JW, and E2FB), because UASMS1 and UASMS3 were completely linked. A uni-variate mixed-inheritance animal model was used to evaluate the association of either genotypes or haplo-types with the traits. The two leptin exon 2 SNP were associated with fat and lean yield and grade fat (E2JW, P < 0.01; E2FB, P < 0.05), and they interacted in their effect on LM tenderness (P < 0.01). The leptin promoter SNP were either not associated with any of the traits (UASMS2) or with fat yield only (UASMS1). Three haplotypes (TCAC, CCAT, TTAC) were at high frequency in the population (88%) and had similar effects on all the traits. Compared with the common haplotypes, one haplotype (CCTT) showed a significantly different effect on fat and lean yield and grade fat (P < 0.01), and one haplotype (TTTT) had a different effect on LM tenderness (P < 0.03). Therefore, important associations between SNP within the leptin gene with lean yield, fatness (fat yield and subcutaneous fat), and tenderness were detected. Results confirm some of the previously reported associations, but diverge with respect to others, showing that further efforts are required to validate some prospective associations.

Adipose Tissue↗

Neuroepithelial bodies not connected to pulmonary slowly adapting stretch receptors.

Neuroepithelial bodies (NEBs) are believed to be connected with one of the known types of airway receptors. The present studies determined whether NEB afferents are pulmonary slowly adapting stretch receptors (SARs). NEBs are immunoreactive with antibodies against protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP), whereas SARs are reactive with antibody to Na(+)/K(+)-ATPase. Using histochemical staining in combination with confocal microscopy, we compared the morphology of NEBs and SARs in the rat. Our results show that NEBs and SARs are different in location, size, and shape. Double staining of airway tissues for PGP (or CGRP) plus Na(+)/K(+)-ATPase shows that NEBs and SARs do not co-localize. In addition, we electrophysiologically recorded single-unit activity of SARs from the cervical vagus nerve, identified their receptive fields, dissected them into blocks, and then double-stained and examined the receptor structures. We found that the blocks contain the SAR, but not NEB structures. Thus, we conclude that NEBs are not connected to SARs.

Animals↗

Filamentation of femtosecond light pulses in the air: turbulent cells versus long-range clusters.

The filamentation of ultrashort pulses in air is investigated theoretically and experimentally. From the theoretical point of view, beam propagation is shown to be driven by the interplay between random nucleation of small-scale cells and relaxation to long waveguides. After a transient stage along which they vary in location and in amplitude, filaments triggered by an isotropic noise are confined into distinct clusters, called "optical pillars," whose evolution can be approximated by an averaged-in-time two-dimensional (2D) model derived from the standard propagation equations for ultrashort pulses. Results from this model are compared with space- and time-resolved numerical simulations. From the experimental point of view, similar clusters of filaments emerge from the defects of initial beam profiles delivered by the Teramobile laser facility. Qualitative features in the evolution of the filament patterns are reproduced by the 2D reduced model.

Journal Article↗

Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line.

The interleukin-mediated Janus kinase (JAK)/STAT pathway plays a crucial role in carcinogenesis. Recently, increased STAT3 activity was found in hepatocellular carcinoma and multiple myeloma in which there was silencing of SOCS-1 (suppressor of cytokine signalling-1) by gene promoter hypermethylation. We investigated the expression level of interleukin-6 (IL-6) and SOCS-1 in gastric cancer cell lines. Expression of SOCS-1 correlated with IL-6 level in most of the cell lines, except for AGS cells in which SOCS-1 was absent despite a high level of IL-6 production. Methylation analysis by methylation-specific polymerase chain reaction and bisulphite sequencing revealed that CpG island of SOCS-1 was densely methylated in AGS cells. Demethylation treatment by 5'aza-deoxycytidine restored SOCS-1 expression and also suppressed constitutive STAT3 phosphorylation in AGS cells. Moreover, methylation of SOCS-1 was detected in 27.5% (11 of 40) of primary gastric tumours samples, 10% (one of 10) of adjacent noncancer tissues but not in any (zero of nine) normal gastric mucosa. Methylation of SOCS-1 also correlated with the loss of mRNA expression in some primary gastric cancers. In conclusion, this is the first report to demonstrate that hypermethylation of SOCS-1 led to gene silencing in gastric cancer cell line and primary tumour samples. Downregulation of SOCS-1 cooperates with IL-6 in the activation of JAK/STAT pathway in gastric cancer.

Carrier Proteins↗

RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer.

Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours of similar stage remains unclear. We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance.

Base Sequence↗

Multiple filamentation of terawatt laser pulses in air.

The filamentation of femtosecond light pulses in air is numerically and experimentally investigated for beam powers reaching several TW. Beam propagation is shown to be driven by the interplay between intense, robust spikes created by the defects of the input beam and random nucleation of light cells. Evolution of the filament patterns can be qualitatively reproduced by an averaged-in-time (2D+1)-dimensional model derived from the propagation equations for ultrashort pulses.

Journal Article↗

Metabolic control analysis as a mechanism that conserves genetic variance during advanced cycle breeding.

The recycling of elite inbreds (i.e., advanced cycle breeding) has led to significant genetic gains but also to a narrow gene pool in plant breeding programs. Sustained yield improvements in many crops have suggested that genetic variance is not depleted at a rate predicted by an additive genetic model. Unlike the additive model in classical quantitative genetic theory, metabolic control analysis relates the variation in a biochemical process with the genetic variation in a quantitative trait. Our objective was to determine whether metabolic control analysis is a mechanism that slows the decrease in genetic variance during advanced cycle breeding. Three cycles of advanced cycle breeding were simulated with 10, 50, or 100 quantitative trait loci (QTL) controlling a trait. In metabolic control analysis, these QTL coded for enzymes involved in a linear metabolic pathway that converted a substrate into a product. In the absence of selection, both the additive model and the metabolic control analysis model led to about a 50% reduction in genetic variance from cycle to cycle. With selection, the additive model led to a 50-58% reduction in genetic variance, but the metabolic control analysis model generally led to only a 12-54% reduction. We suggest selection in a metabolic control analysis model as a mechanism that slows the decrease in genetic variance during advanced cycle breeding. This conservation of genetic variance would allow breeders to achieve genetic gains for a longer period than expected under the additive model.

Conserved Sequence↗

Identification and molecular characterization of a novel y-type Glu-Dt 1 glutenin gene of Aegilops tauschii.

A novel y-type high-molecular-weight glutenin subunit possessing a slightly faster mobility than that of subunit 1Dy12 in SDS-PAGE, designated 1Dy12.1(t) in Aegilops tauschi, was identified by one- and two-dimensional gel and capillary electrophoresis. Its coding gene at the Glu-D(t) 1 locus was amplified with allele-specific-PCR primers, and the amplified products were cloned and sequenced. The complete nucleotide sequence of 2,807 bp containing an open reading frame of 1,950 bp and 857 bp of upstream sequence was obtained. A perfectly conserved enhancer sequence and the -300 element were present at positions of 209-246 bp and 424-447 bp upstream of the ATG start codon, respectively. The deduced mature protein of 1 Dy12.1(t) subunit comprised 648 amino acid residues and had a Mr of 67,518 Da, which is slightly smaller than the 1Dy12 (68,695 Da) but larger than the 1Dy10 (67,495 Da) subunits of bread wheat, respectively, and corresponds well with their relative mobilities when separated by acid-PAGE. The deduced amino acid sequence indicated that the 1Dy12.1(t) subunit displayed a greater similarity to the 1Dy10 subunit, with only seven amino acid substitutions, suggesting that this novel gene could have positive effect on bread-making quality. A phenetic tree produced by nucleotide sequences showed that the x- and y-type subunit genes were respectively clustered together and that the Glu-D(t) 1y12.1 gene of Ae. tauschii is closely related to other y-type subunit genes from the B and D genomes of hexaploid bread wheat.

Agriculture↗

From disease genes to cellular pathways: a progress report.

Mutations in a large number of retinal and retinal pigment epithelium (RPE) expressed genes can lead to the degeneration of photoreceptors and consequently the loss of vision. The genetic and phenotypic heterogeneity of retinal dystrophies poses a complex problem with respect to rational development of therapeutic strategies. Delineation of physiological functions of disease genes and identification of pathways that lead to disease pathogenesis represent essential goals towards developing a systematic and global approach to gene-based treatments. We are interested in identifying cellular pathways that are involved in photoreceptor differentiation, function and degeneration. We are, therefore, generating comprehensive gene expression profiles of retina and RPE of humans and mice using both cDNA- and oligonucleotide-based (Affymetrix) microarrays. Because of the under-representation of retinal/RPE genes in the public databases, we have constructed several unamplified cDNA libraries and produced almost twenty thousand expressed sequence tags (ESTs) that are being printed onto glass slides ('I-Gene' microarrays). In this presentation, we will report the microarray analysis of the rodless (and cone-enhanced) retina from the Nrl-knockout mouse as a paradigm to initiate the identification of cellular pathways involved in photoreceptor differentiation and function.

DNA-Binding Proteins↗

Single-acquisition sequence for the measurement of oxygen partial pressure by hyperpolarized gas MRI.

Magnetic resonance imaging (MRI) with hyperpolarized 3-helium gas (HP 3He) offers the possibility of studying functional lung parameters such as the alveolar oxygen concentration and oxygen depletion rate. Until now, a double-acquisition technique has been utilized to extract these parameters. A complicated single-acquisition technique was previously developed to avoid the necessity of performing two identical breathing maneuvers. The results obtained with this technique were significantly less accurate than the results obtained with the double-acquisition method. In this work, a novel, easily implemented single-acquisition sequence is presented that provides results comparable to those obtained with the established double-acquisition method. This method is demonstrated in a phantom and a pig model on a 1.5 T scanner using a 2D fast low-angle shot (FLASH) gradient-echo sequence. Numerical simulations of the time evolution of the oxygen concentration were performed. Simulation results are presented to support the experimental data. Various parameter regimes were experimentally and numerically investigated.

Animals↗